The present research project is designed to utilize the pentobarbital pellet implantation techniques developed in our laboratory for the study of biochemical mechanisms in barbiturate tolerance and dependence. Studies are undertaken on the contributory role of putative neurotransmitters involved in acute pentobarbital effects and in the development of tolerance to and physical dependence on barbiturates. Studies are also carried out on the applic ation of this model for investigating the interactions of continuous administrat ion of barbiturates with other drugs of abuse. The specific research plans are: (1) systematic quantification of tolerance and dependence by using pellet implantation; (2) assessment of the contributory role of putative neurotransmitters in the central nervous system involved in acute pentobarbitale effect and during the development of tolerance and physical dependence; (3) assessment of the effect of pharmacological manipulation on the development of pentobarbital tolerance and physical dependence; (4) assessment of heptic drug metabolizing enzyme inhibitor such as procarbazine on pentobarbital toleranc e and dependence; (5) application of this mode for studying the interaction of continuous administration of barbiturates nd other drugs of abuse such as non-barbiturate type sedative hypnotics, benzodiazopines, ketamine and alcohol; and (6) application of a similar technique to study the long-acting barbiturate, barbital, to examine if there is a common mechanism in terms of CNS tolerance to and physical dependence on barbiturates.